Abstract
RNA N4-acetylcytidine (ac4C) is a highly conserved RNA modification that plays a crucial role in controlling mRNA stability, processing, and translation. Consequently, accurate identification of ac4C sites across the genome is critical for understanding gene expression regulation mechanisms. In this study, we have developed ac4C-AFL, a bioinformatics tool that precisely identifies ac4C sites from primary RNA sequences. In ac4C-AFL, we identified the optimal sequence length for model building and implemented an adaptive feature representation strategy that is capable of extracting the most representative features from RNA. To identify the most relevant features, we proposed a novel ensemble feature importance scoring strategy to rank features effectively. We then used this information to conduct the sequential forward search, which individually determine the optimal feature set from the 16 sequence-derived feature descriptors. Utilizing these optimal feature descriptors, we constructed 176 baseline models using 11 popular classifiers. The most efficient baseline models were identified using the two-step feature selection approach, whose predicted scores were integrated and trained with the appropriate classifier to develop the final prediction model. Our rigorous cross-validations and independent tests demonstrate that ac4C-AFL surpasses contemporary tools in predicting ac4C sites. Moreover, we have developed a publicly accessible web server at https://balalab-skku.org/ac4C-AFL/.